Ethylphenacemide and phenacemide: conformational similarities to diphenylhydantoin and stereochemical basis of anticonvulsant activity.

The three-dimensional molecular structures of the potent anticonvulsant agents phenacemide and ethylphenacemide have been determined by single-crystal x-ray diffraction. Although these compounds possess straight-chain acetylurea groupings, in the crystalline state both molecules adopt a pseudocyclic conformation of the acetylurea chain through amide...carbonyl oxygen intramolecular hydrogen bonding. This results in spatial positioning and relative orientation of two electron-donating functional groups in these molecules similar to those of comparable atoms in diphenylhydantoin and other heterocycle-containing anticonvulsants.